Artículos de revistas
Uncovering false positives on a virtual screening search for cruzain inhibitors
Fecha
2008Registro en:
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, v.18, n.1, p.350-354, 2008
0960-894X
10.1016/j.bmcl.2007.10.068
Autor
MALVEZZI, Alberto
REZENDE, Leandro de
IZIDORO, Mario Augusto
CEZARI, Maria Helena Sedenho
JULIANO, Luiz
AMARAL, Antonia T. -Do
Institución
Resumen
Some unexpected promiscuous inhibitors were observed in a virtual screening protocol applied to select cruzain inhibitors from the ZINC database. Physical-chemical and pharmacophore model filters were used to reduce the database size. The selected compounds were docked into the cruzain active site. Six hit compounds were tested as inhibitors. Although the compounds were designed to be nucleophilically attacked by the catalytic cysteine of cruzain, three of them showed typical promiscuous behavior, revealing that false positives are a prevalent concern in VS programs. (C) 2007 Elsevier Ltd. All rights reserved.